2011 Diagnostic Slide Session
Case 7
Aditya Raghunathan
Suzanne Z. Powell
Presentation
47 year old woman
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Altered mental status
HIV diagnosed in 1993
NOT taken therapy ~ 14 yrs
Past medical history: Shingles
On admission: CD4 20 cells/ μL
Mediastinal mass
MRI
T2
FLAIR
Mediastinal
Mass
Adenomatous
hyperplasia
(Multinodular goiter)
Subsequently,
frontal lobe lesions were
biopsied...
Intra-Operative Cytology
DIAGNOSIS?
LFB-PAS
GFAP
Additional Studies
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HSV 1, HSV2, CMV, EBV, Enterovirus
IHC & culture : Negative
BK virus IHC, JC virus-ISH: Negative
Toxoplasma IHC: Negative
Bacterial/ fungal stains & cultures:
Negative
HHV3 (VZV) Immunostain
Electron Microscopy
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VZV Immunostain positive
PCR: VZV DNA detected
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Measles IHC/ PCR: Negative
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Human herpes virus 3
encephalitis/
vasculopathy
(HHV3, Varicella zoster virus)
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In the context of an HIV+ patient,
untreated for 14 years
HIV in the HAART Era
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Epidemiologically ↓ “main” opportunistic inf.
e.g. Toxoplasmosis, Cryptococcal meningitis
↑ Nonspecific/ nonlethal CNS diseases
↑ Uncommon CNS infections
 VZV & HSV
Gray F et al. (2003)
CNS Symptoms & CSF VZV Load
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Immunocompromised: Deeper sites
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Small-vessel vasculopathy, meningoencephalitis,
ventriculitis & myelitis
97 cases: ↑ CSF VZV DNA load in encephalitis &
acute aseptic meningitis
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> Cranial nerve disease
Kleinschmidt-DeMasters BK et al. (2001)
Persson A et al. (2009)
VZV Detection
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Highly cell associated
Present in low titers
Culture from CSF rarely +
In CSF, diagnostic value of detecting
anti-VZV IgG antibodies > VZV DNA
Nagel et al. (2007)
VZV Genotypes
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4021 patients w. ? CNS VZV infection
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43 + VZV DNA in CSF by PCR
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CNS disease frequently w/o rash
Can resemble HSV encephalitis
7 genotypes identified at CDC
 1 Oka vaccine strain
 ? Vaccine - associated CNS disease
Pahlud et al. (2011)
References
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Pahud BA, Glaser CA, Dekker CL, Arvin AM, Schmid DS.
Varicella zoster disease of the central nervous system:
epidemiological, clinical, and laboratory features 10 years after
the introduction of the varicella vaccine. J Infect Dis. 2011
Feb 1;203(3):316-23.
Gray F, Chrétien F, Vallat-Decouvelaere AV, Scaravilli F. The
changing pattern of HIV neuropathology in the HAART era. J
Neuropathol Exp Neurol. 2003 May;62(5):429-40.
Kleinschmidt-DeMasters BK, Gilden DH. Varicella-Zoster virus
infections of the nervous system: clinical and pathologic
correlates. Arch Pathol Lab Med. 2001;125:770-80
Nagel MA, Forghani B, Mahalingam R, et al.: The value of
detecting anti-VZV IgG antibody in CSF to diagnose VZV
vasculopathy. Neurology 2007, 68:1069–1073.
Persson A, Bergström T, Lindh M, Namvar L, Studahl M.
Varicella-zoster virus CNS disease--viral load, clinical
manifestations and sequels. J Clin Virol. 2009 Nov;46(3):24953.
Thank You!